CTNNB1 (Catenin, beta-1)
2002-03-01 Brigitte Debuire , Antoinette Lemoine , Raphael Saffroy AffiliationService de Biochimie et Biologie moléculaire, Hôpital Universitaire Paul Brousse, UPRES 1596-Faculté de Médecine Paris-Sud, 14 avenue Paul Vaillant Couturier, 94804 Villejuif Cedex, France
Identity
HGNC
LOCATION
3p22.1
IMAGE
LEGEND
CTNNB1 (3p22) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
LOCUSID
ALIAS
CTNNB,EVR7,MRD19,NEDSDV,armadillo
FUSION GENES
DNA/RNA
Description
The gene encompasses 23.2kb of DNA ; 16 exons (the first is non-coding).
Transcription
3362 nucleotides mRNA ; 2343 bp open reading frame. Alternative splicing within exon 16 produces a splice variant that is 159 bp shorter in the 3 untranslated region.
Proteins
Description
781 amino acids ; 92 kDa protein. Can be phosphorylated ; contains from N-term to C-term, a phosphorylation site by the serine-threonine glycogen synthase kinase -3b(GSK-3b), an a-catenin binding site, 13 armadillo repeats and a transactivating domain.
Expression
Widely expressed.
Localisation
Cytoplasm and nucleus
Function
Important functions in the E-cadherin-mediated cell-cell adhesion system and also as a dowstream signaling molecule in the Wnt pathway. Cytoplasmic accumulation of b catenin allows it to translocate to the nucleus to form complexes with transcription factors of the T cell factor-lymphoid enhancer factor (Tcf-Lef) family. b-catenin is assumed to transactivate mostly unknown target genes, which may stimulate cell proliferation (acts as an oncogene) or inhibit apoptosis. The b-catenin level in the cell is regulated by its association with the adenomatous polyposis coli ( APC) tumor suppressor protein, axin and GSK-3b. Phosphorylation of b-catenin by the APC-axin-GSK-3b complex leads to its degradation by the ubiquitin-proteasome system.
Homology
The b-catenin protein shares 70 % amino acid identity with both plakoglobin (intracellular junction in desmosomes) and the product of the Drosphila segment polarity gene "armadillo".
Mutations
Somatic
Two mechanisms underlying the increase in b-catenin levels by stabilizing b-catenin are known. One is inactivating mutation in the APC gene, the other is activating mutation at the GSK-3b phosphorylation sites within exon 3 of the b-catenin gene.
b-catenin plays a key role in the development of colorectal cancer and has been found mutated in colorectal cancer cell lines. b-catenin aberration is a frequent event in the development of hepatocellular carcinoma and may facilitate its development in the course of chronic hepatitis. b-catenin has also been found mutated in hepatoblastoma, ovarian carcinoma, medulloblastoma, pilomatricoma as well as in melanoma cell lines.
b-catenin plays a key role in the development of colorectal cancer and has been found mutated in colorectal cancer cell lines. b-catenin aberration is a frequent event in the development of hepatocellular carcinoma and may facilitate its development in the course of chronic hepatitis. b-catenin has also been found mutated in hepatoblastoma, ovarian carcinoma, medulloblastoma, pilomatricoma as well as in melanoma cell lines.
Implicated in
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 9233789 | 1997 | beta-catenin is a target for the ubiquitin-proteasome pathway. | Aberle H et al |
| 7780664 | 1995 | Yeast artificial chromosome cloning of the beta-catenin locus on human chromosome 3p21-22. | Bailey A et al |
| 9554852 | 1998 | Functional interaction of an axin homolog, conductin, with beta-catenin, APC, and GSK3beta. | Behrens J et al |
| 8757136 | 1996 | Functional interaction of beta-catenin with the transcription factor LEF-1. | Behrens J et al |
| 10398436 | 1999 | Beta-catenin accumulation and mutation of the CTNNB1 gene in hepatoblastoma. | Bläker H et al |
| 10192393 | 1999 | A common human skin tumour is caused by activating mutations in beta-catenin. | Chan EF et al |
| 10362259 | 1999 | The metalloproteinase matrilysin is a target of beta-catenin transactivation in intestinal tumors. | Crawford HC et al |
| 9501980 | 1998 | Nuclear localization signal-independent and importin/karyopherin-independent nuclear import of beta-catenin. | Fagotto F et al |
| 11282485 | 2001 | Frequent beta-catenin aberration in human hepatocellular carcinoma. | Fujie H et al |
| 8573337 | 1995 | Signal transduction of beta-catenin. | Gumbiner BM et al |
| 10545105 | 1999 | Intestinal polyposis in mice with a dominant stable mutation of the beta-catenin gene. | Harada N et al |
| 9601641 | 1998 | Downregulation of beta-catenin by human Axin and its association with the APC tumor suppressor, beta-catenin and GSK3 beta. | Hart MJ et al |
| 10666372 | 2000 | APC mutations in sporadic medulloblastomas. | Huang H et al |
| 8892228 | 1996 | Nuclear localization of beta-catenin by interaction with transcription factor LEF-1. | Huber O et al |
| 9482734 | 1998 | Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin. | Ikeda S et al |
| 9294210 | 1997 | Beta-catenin mutations in cell lines established from human colorectal cancers. | Ilyas M et al |
| 9500465 | 1998 | Activation of the beta-catenin gene by interstitial deletions involving exon 3 in primary colorectal carcinomas without adenomatous polyposis coli mutations. | Iwao K et al |
| 9927029 | 1999 | Childhood hepatoblastomas frequently carry a mutated degradation targeting box of the beta-catenin gene. | Koch A et al |
| 10953028 | 2000 | Gastrin is a target of the beta-catenin/TCF-4 growth-signaling pathway in a model of intestinal polyposis. | Koh TJ et al |
| 7829088 | 1994 | Localization of the human beta-catenin gene (CTNNB1) to 3p21: a region implicated in tumor development. | Kraus C et al |
| 10435629 | 1999 | Beta-catenin mutations in hepatocellular carcinoma correlate with a low rate of loss of heterozygosity. | Legoix P et al |
| 11017067 | 2000 | Mutations in AXIN2 cause colorectal cancer with defective mismatch repair by activating beta-catenin/TCF signalling. | Liu W et al |
| 11711551 | 2002 | The transcriptional factor Tcf-4 contains different binding sites for beta-catenin and plakoglobin. | Miravet S et al |
| 9065402 | 1997 | Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. | Morin PJ et al |
| 8838805 | 1996 | Genomic organization of the human beta-catenin gene (CTNNB1). | Nollet F et al |
| 11781281 | 2002 | Oncogenic beta-catenin and MMP-7 (matrilysin) cosegregate in late-stage clinical colon cancer. | Ougolkov AV et al |
| 9065403 | 1997 | Stabilization of beta-catenin by genetic defects in melanoma cell lines. | Rubinfeld B et al |
| 10391090 | 1999 | Mutational analysis of beta-catenin gene in Japanese ovarian carcinomas: frequent mutations in endometrioid carcinomas. | Sagae S et al |
| 11796830 | 2002 | Possible association between higher beta-catenin mRNA expression and mutated beta-catenin in sporadic desmoid tumors: real-time semiquantitative assay by TaqMan polymerase chain reaction. | Saito T et al |
| 10318916 | 1999 | The cyclin D1 gene is a target of the beta-catenin/LEF-1 pathway. | Shtutman M et al |
| 9515795 | 1998 | Mutational analysis of the APC/beta-catenin/Tcf pathway in colorectal cancer. | Sparks AB et al |
| 8259519 | 1993 | Association of the APC tumor suppressor protein with catenins. | Su LK et al |
| 11786918 | 2002 | Frizzled-10, up-regulated in primary colorectal cancer, is a positive regulator of the WNT - beta-catenin - TCF signaling pathway. | Terasaki H et al |
| 8521721 | 1995 | The gene for the APC-binding protein beta-catenin (CTNNB1) maps to chromosome 3p22, a region frequently altered in human malignancies. | Trent JM et al |
| 9671767 | 1998 | Somatic mutations of the beta-catenin gene are frequent in mouse and human hepatocellular carcinomas. | de La Coste A et al |
| 7736793 | 1995 | Assignment of the human beta-catenin gene (CTNNB1) to 3p22-->p21.3 by fluorescence in situ hybridization. | van Hengel J et al |
Other Information
Locus ID:
NCBI: 1499
MIM: 116806
HGNC: 2514
Ensembl: ENSG00000168036
Variants:
dbSNP: 1499
ClinVar: 1499
TCGA: ENSG00000168036
COSMIC: CTNNB1
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
PharmGKB
| Entity ID | Name | Type | Evidence | Association | PK | PD | PMIDs |
|---|---|---|---|---|---|---|---|
| PA162363968 | lenalidomide | Chemical | ClinicalAnnotation | associated | PD | 26521987 | |
| PA444985 | Multiple Myeloma | Disease | ClinicalAnnotation | associated | PD | 26521987 | |
| PA448871 | celecoxib | Chemical | Pathway | associated | 22336956 | ||
| PA449165 | cyclophosphamide | Chemical | ClinicalAnnotation | associated | PD | 26521987 | |
| PA449247 | dexamethasone | Chemical | ClinicalAnnotation | associated | PD | 26521987 | |
| PA451644 | thalidomide | Chemical | ClinicalAnnotation | associated | PD | 26521987 |
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37278959 | 2024 | MiR-138-5p Inhibits Thyroid Cancer Cell Growth and Stemness by Targeting TRPC5/Wnt/β-Catenin Pathway. | 0 |
| 37649322 | 2024 | Correlation between E-cadherin/β-catenin, Vimentin expression, clinicopathologic features and drug resistance prediction in naïve prostate cancer: A molecular and clinical study. | 0 |
| 37820851 | 2024 | PFKFB3 promotes endometriosis cell proliferation via enhancing the protein stability of β-catenin. | 0 |
| 37870288 | 2024 | Wnt/β-catenin and NFκB signaling synergize to trigger growth factor-free regeneration of adult primary human hepatocytes. | 1 |
| 37953090 | 2024 | Targeted next-generation sequencing of Japanese patients with sinonasal mucosal melanomas identifies frequent NRAS and CTNNB1 mutations. | 0 |
| 37963200 | 2024 | CircMMP2(6,7) Cooperates with β-Catenin and PRMT5 to Disrupt Bone Homeostasis and Promote Breast Cancer Bone Metastasis. | 1 |
| 38043628 | 2024 | METTL3 regulates FAM83D m(6)A modification to accelerate tumorigenesis of triple-negative breast cancer via the Wnt/β-catenin pathway. | 2 |
| 38069565 | 2024 | USP14 promotes the proliferation of cervical cancer via upregulating β-catenin. | 0 |
| 38069906 | 2024 | Metabolic modulation of histone acetylation mediated by HMGCL activates the FOXM1/β-catenin pathway in glioblastoma. | 0 |
| 38184500 | 2024 | 27-Hydroxycholesterol activates the GSK-3β/β-catenin signaling pathway resulting in intestinal fibrosis by inducing oxidative stress: effect of dietary interventions. | 0 |
| 38247296 | 2024 | Clinical phenotypic spectrum of CTNNB1 neurodevelopmental disorder. | 0 |
| 38297082 | 2024 | PARP1-stabilised FOXQ1 promotes ovarian cancer progression by activating the LAMB3/WNT/β-catenin signalling pathway. | 0 |
| 38311851 | 2024 | DLK1/DIO3 locus upregulation by a β-catenin-dependent enhancer drives cell proliferation and liver tumorigenesis. | 1 |
| 38324534 | 2024 | β-catenin mediates growth defects induced by centrosome loss in a subset of APC mutant colorectal cancer independently of p53. | 0 |
| 38364252 | 2024 | miR-557 inhibits hepatocellular carcinoma progression through Wnt/β-catenin signaling pathway by targeting RAB10. | 1 |
Citation
Brigitte Debuire ; Antoinette Lemoine ; Raphael Saffroy
CTNNB1 (Catenin, beta-1)
Atlas Genet Cytogenet Oncol Haematol. 2002-03-01
Online version: http://atlasgeneticsoncology.org/gene/71
